C.B. Hess

Radiation-Induced Dedifferentiation of Head and Neck Cancer Cells Into Cancer Stem Cells Depends on Human Papillomavirus Status.

PURPOSE To test the hypothesis that the radiation response of cancer stem cells (CSCs) in human papillomavirus (HPV)-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) differs and is not reflected in the radiation response of the bulk tumor populations, that radiation therapy (RT) can dedifferentiate non-stem HNSCC cells into CSCs, and that radiation-induced dedifferentiation depends on the HPV status. METHODS AND MATERIALS Records of a cohort of 162 HNSCC patients were reviewed, and their outcomes were correlated with their HPV status. Using a panel of HPV-positive and HPV-negative HNSCC cell lines expressing a reporter for CSCs, we characterized HPV-positive and HPV-negative lines via flow cytometry, sphere-forming capacity assays in vitro, and limiting dilution assays in vivo. Non-CSCs were treated with different doses of radiation, and the dedifferentiation of non-CSCs into CSCs was investigated via flow cytometry and quantitative reverse transcription-polymerase chain reaction for re-expression of reprogramming factors. RESULTS Patients with HPV-positive tumors have superior overall survival and local-regional control. Human papillomavirus-positive HNSCC cell lines have lower numbers of CSCs, which inversely correlates with radiosensitivity. Human papillomavirus-negative HNSCC cell lines lack hierarchy owing to enhanced spontaneous dedifferentiation. Non-CSCs from HPV-negative lines show enhanced radiation-induced dedifferentiation compared with HPV-positive lines, and RT induced re-expression of Yamanaka reprogramming factors. CONCLUSIONS Supporting the favorable prognosis of HPV-positive HNSCCs, we show that (1) HPV-positive HNSCCs have a lower frequency of CSCs; (2) RT can dedifferentiate HNSCC cells into CSCs; and (3) radiation-induced dedifferentiation depends on the HPV status of the tumor.

Measuring psychosocial functioning in the radiation oncology clinic: a systematic review†

This paper aimed to systematically review the (1) prevalence, (2) risk factors, (3) interventions, and (4) measurement instruments associated with psychosocial function decline in radiation therapy (RT) patients.

Competing Causes of Death and Medical Comorbidities Among Patients With Human Papillomavirus-Positive vs Human Papillomavirus-Negative Oropharyngeal Carcinoma and Impact on Adherence to Radiotherapy

IMPORTANCE Survival of patients with head and neck cancer can be affected by competing causes of mortality, as well as comorbidities that result in radiation treatment interruptions. OBJECTIVE To discern how differences in preexisting medical and psychosocial comorbidities potentially influence adherence to radiation therapy according to human papillomavirus (HPV) status. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis at a comprehensive cancer center of 162 consecutive patients with locally advanced squamous cell carcinoma of the oropharynx treated with primary chemoradiation (n = 95) or primary surgery followed by adjuvant radiation (n = 67). Immunostaining for p16 was used to determine HPV status. MAIN OUTCOMES AND MEASURES Difference in alcohol, tobacco, and marijuana use was compared between patients with HPV-positive and HPV-negative tumors, as well as the prevalence of the following comorbidities: diabetes mellitus, chronic obstructive pulmonary disease (COPD), anxiety disorder, and major depression. The number of total missed treatment days was analyzed as both a continuous and categorical variable. RESULTS Rates of self-reported heavy alcohol use (47% vs 16%; P = .02) and any marijuana use (47% vs 23%; P = .003) were significantly higher among HPV-negative patients. Fifty-four percent of HPV-positive patients self-identified as never smokers, compared with only 12% of HPV-negative patients (P < .001). HPV-negative patients had more missed treatment days (mean, 2.8 vs 1.7 days; P = .02), as well as an increased rate of at least 5 missed days (24% vs 10%; P = .04), and higher prevalences of COPD (12% vs 7%; P = .37) and anxiety disorder (12% vs 6%; P = .35). CONCLUSIONS AND RELEVANCE Pronounced differences exist in lifestyle habits between patients with HPV-negative and HPV-positive oropharyngeal cancer at diagnosis. These differences, as well as those of medical and psychosocial burden, may contribute to observed discrepancies in treatment adherence and need to be considered in outcomes reporting and clinical trial design.

Identification of Stage I Non-small Cell Lung Cancer Patients at High Risk for Local Recurrence Following Sublobar Resection

OBJECTIVE An increasing proportion of patients with stage I non-small cell lung cancer (NSCLC) is undergoing sublobar resection (L-). However, there is little information about the risks and correlates of local recurrence (LR) after such surgery, especially compared with patients undergoing lobectomy (L+). METHODS Ninety-three and 318 consecutive patients with stage I NSCLC underwent L- and L+, respectively, from 2000 to 2006. Median follow-up was 34 months. RESULTS In the L- group, the LR rates at 2, 3, and 5 years were 13%, 24%, and 40%, respectively. The risk of LR was significantly associated with tumor grade, tumor size, and T stage. The crude risk of LR was 33.8% (21 of 62) for patients whose tumors were grade ≥ 2. In the L+ group, the LR rates at 2, 3, and 5 years were 14%, 19%, and 24%, respectively. The risk of LR significantly increased with increasing tumor size, length of hospital stay, and the presence of diabetes. The L- group experienced a significant increase in failure in the bronchial stump/staple line compared with the L+ group (10% vs 3%; P = .04) and nonsignificant trends toward increased ipsilateral hilar and subcarinal failure rates. CONCLUSIONS Patients with stage I NSCLC who undergo L- have an increased risk of LR compared with patients undergoing L+, particularly when they have tumors grade ≥ 2 or tumor size > 2 cm. If L- is considered, additional local therapy should be considered to reduce this risk of LR, especially with tumors grade ≥ 2 or size > 2 cm.

Socioeconomic and Racial Disparities in the Selection of Chest Wall Boost Radiation Therapy in Californian Women After Mastectomy

UNLABELLED To better elucidate the socioeconomic and racial differences in women who received postmastectomy radiation therapy with or without a chest wall boost, the records from 4747 women included in the California Cancer Registry were reviewed. Poor and Hispanic women were more likely to receive a chest wall boost than were more affluent and non-Hispanic women. INTRODUCTION Healthcare disparities in breast cancer treatment have been well documented. We investigated the socioeconomic status (SES) and racial factors in women with locally advanced breast cancer from the California Cancer Registry who had received postmastectomy radiation therapy (PMRT) with or without a chest wall boost (CWB). PATIENTS AND METHODS The records of 4747 women with invasive breast cancer, diagnosed from 2005 to 2009, who had undergone PMRT, were reviewed and stratified by treatment with (n = 2686 [57%]) or without (n = 2061 [43%]) a CWB. Various patient demographic and biologic factors were analyzed using univariate and multivariate analysis. RESULTS Receipt of a CWB was associated with race/ethnicity (P < .001), SES (P < .001), tumor size (P = .038), tumor grade (P = .033), human epidermal growth factor 2 (HER2) status (P = .015), American Joint Committee on Cancer stage (P = .001), number of nodes examined (P = .001), and number of positive nodes (P = .037) on univariate analysis. After controlling for confounding factors, race/ethnicity and SES remained independently predictive of a CWB. Hispanic women were more likely to receive a CWB than Asian (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.60-0.90), black (HR, 0.63; 95% CI, 0.48-0.83), or white (HR, 0.81; 95% CI, 0.69-0.95) women. Also, women of low SES were more likely to receive a CWB than women of high SES (HR, 0.74; 95% CI, 0.64-0.86). CONCLUSION We found that poor and Hispanic women were more commonly treated with a CWB than were more affluent and non-Hispanic women with a similar cancer stage, cancer biology, and treatment paradigm.

Characterization and evaluation of an integrated quality monitoring system for online quality assurance of external beam radiation therapy

Abstract Purpose The aim of this work was to comprehensively evaluate a new large field ion chamber transmission detector, Integral Quality Monitor (IQM), for online external photon beam verification and quality assurance. The device is designed to be mounted on the linac accessory tray to measure and verify photon energy, field shape, gantry position, and fluence before and during patient treatment. Methods Our institution evaluated the newly developed ion chambers effect on photon beam fluence, response to dose, detection of photon fluence modification, and the accuracy of the integrated barometer, thermometer, and inclinometer. The detection of photon fluence modifications was performed by measuring 6 MV with fields of 10 cm × 10 cm and 1 cm × 1 cm “correct” beam, and then altering the beam modifiers to simulate minor and major delivery deviations. The type and magnitude of the deviations selected for evaluation were based on the specifications for photon output and MLC position reported in AAPM Task Group Report 142. Additionally, the change in ion chamber signal caused by a simulated IMRT delivery error is evaluated. Results The device attenuated 6 MV, 10 MV, and 15 MV photon beams by 5.43 ± 0.02%, 4.60 ± 0.02%, and 4.21 ± 0.03%, respectively. Photon beam profiles were altered with the IQM by < 1.5% in the nonpenumbra regions of the beams. The photon beam profile for a 1 cm × 1 cm2 fields were unchanged by the presence of the device. The large area ion chamber measurements were reproducible on the same day with a 0.14% standard deviation and stable over 4 weeks with a 0.47% SD. The ion chambers dose–response was linear (R2 = 0.99999). The integrated thermometer agreed to a calibrated thermometer to within 1.0 ± 0.7°C. The integrated barometer agreed to a mercury barometer to within 2.3 ± 0.4 mmHg. The integrated inclinometer gantry angle measurement agreed with the spirit level at 0 and 180 degrees within 0.03 ± 0.01 degrees and 0.27 ± 0.03 at 90 and 270 degrees. For the collimator angle measurement, the IQM inclinometer agreed with a plum‐bob within 0.3 ± 0.2 degrees. The simulated IMRT error increased the ion chamber signal by a factor of 11–238 times the baseline measurement for each segment. Conclusions The device signal was dependent on variations in MU delivered, field position, single MLC leaf position, and nominal photon energy for both the 1 cm × 1 cm and 10 cm × 10 cm fields. This detector has demonstrated utility repeated photon beam measurement, including in IMRT and small field applications.

Left hippocampal dosimetry correlates with visual and verbal memory outcomes in survivors of pediatric brain tumors: Hippocampal Dosimetry and Memory Post-RT

Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT).

Global and health-related quality of life after intensity-modulated radiation therapy for head and neck cancer

This study aims to evaluate the current literature regarding the effects of conventional radiation therapy (CRT) versus intensity-modulated radiation therapy (IMRT) on global quality of life (QoL) among patients treated for head and neck cancer. A PubMed literature review was performed. Only articles comparing global QoL scores in head and neck cancer patients treated with CRT versus IMRT were included. Studies were scrutinized for methodology, level of evidence and limitations. Outcomes were evaluated for external validity, level of evidence and applicability. Between 2005 and 2012, 14 eligible studies (six prospective, two randomized controlled trials) were identified. Although all presented data comment on the advantages of IMRT, differences in study design made comparisons difficult. The vast majority of these were also limited by relatively small sample sizes and heterogeneity with respect to patient and treatment-related characteristics. Although more robust evidence is needed in the future, the published data reasonably support the benefits of IMRT as compared with CRT (either 2D or 3D) in improving QoL, beginning at approximately 3–6 months post-treatment, and possibly potentiating with time up to 2 and 3 years.

Performance/outcomes data and physician process challenges for practical big data efforts in radiation oncology

It is an exciting time for big data efforts in radiation oncology. The use of big data to help aid both outcomes and decision-making research is becoming a reality. However, there are true challenges that exist in the space of gathering and utilizing performance and outcomes data. Here, we summarize the current state of big data in radiation oncology with respect to outcomes and discuss some of the efforts and challenges in radiation oncology big data.

An update from the Pediatric Proton Consortium Registry

Background/objectives The Pediatric Proton Consortium Registry (PPCR) was established to expedite proton outcomes research in the pediatric population requiring radiotherapy. Here, we introduce the PPCR as a resource to the oncology community and provide an overview of the data available for further study and collaboration. Design/methods A multi-institutional registry of integrated clinical, dosimetric, radiographic, and patient-reported data for patients undergoing proton radiation therapy was conceived in May 2010. Massachusetts General Hospital began enrollment in July of 2012. Subsequently, 12 other institutions joined the PPCR and activated patient accrual, with the latest joining in 2017. An optional patient-reported quality of life (QoL) survey is currently implemented at six institutions. Baseline health status, symptoms, medications, neurocognitive status, audiogram findings, and neuroendocrine testing are collected. Treatment details of surgery, chemotherapy, and radiation therapy are documented and radiation plans are archived. Follow-up is collected annually. Data were analyzed 25 September, 2017. Results A total of 1,854 patients have consented and enrolled in the PPCR from October 2012 until September 2017. The cohort is 55% male, 70% Caucasian, and comprised of 79% United States residents. Central nervous system (CNS) tumors comprise 61% of the cohort. The most common CNS histologies are as follows: medulloblastoma (n = 276), ependymoma (n = 214), glioma/astrocytoma (n = 195), craniopharyngioma (n = 153), and germ cell tumors (n = 108). The most common non-CNS tumors diagnoses are as follows: rhabdomyosarcoma (n = 191), Ewing sarcoma (n = 105), Hodgkin lymphoma (n = 66), and neuroblastoma (n = 55). The median follow-up is 1.5 years with a range of 0.14 to 4.6 years. Conclusion A large prospective population of children irradiated with proton therapy has reached a critical milestone to facilitate long-awaited clinical outcomes research in the modern era. This is an important resource for investigators both in the consortium and for those who wish to access the data for academic research pursuits.